TMTC4 is a transmembrane O-mannosyltransferase that catalyzes the transfer of mannosyl residues to serine and threonine residues on target proteins, primarily cadherins, within the endoplasmic reticulum 1. The protein belongs to the GT-C/PMT sugar transferase superfamily and contains 11 transmembrane domains with conserved catalytic sites for metal ion and dolichyl-phosphate-mannose binding 1. Clinically, TMTC4 loss-of-function is associated with autosomal recessive deafness (DFNB122) through a hair cell-specific mechanism 2. TMTC4-deficient mice exhibit progressive postnatal hearing loss due to overactivation of the unfolded protein response (UPR) and subsequent apoptosis 32. Human TMTC4 variants confer hypersensitivity to UPR-induced apoptosis and segregate with adult-onset progressive hearing loss in affected families 2. Beyond hearing, TMTC4 has emerging roles in other diseases. It serves as a diagnostic biomarker for prostate cancer with 100% sensitivity and 96.6% specificity 4. Conversely, TMTC4 downregulation is associated with improved prognosis in osteosarcoma and may impact cellular proliferation 5. TMTC4 variants also associate with decreased silicosis risk through alternative polyadenylation mechanisms 6, and the gene appears relevant to bone mineral density regulation 7.